1-214403170-C-T

Variant names:

• chr1-214403170-C-T
• rs6657749
• NM_005401.5:c.511-217G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005401.5(PTPN14):​c.511-217G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,106 control chromosomes in the GnomAD database, including 2,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.19 (2990 hom., cov: 32)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.120
• Publications: 6 publications found

Genes affected

PTPN14 (HGNC:9647): (protein tyrosine phosphatase non-receptor type 14) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an N-terminal noncatalytic domain similar to that of band 4.1 superfamily cytoskeleton-associated proteins, which suggested the membrane or cytoskeleton localization of this protein. It appears to regulate lymphatic development in mammals, and a loss of function mutation has been found in a kindred with a lymphedema-choanal atresia. [provided by RefSeq, Sep 2010]

PTPN14 Gene-Disease associations (from GenCC):

• lymphedema-posterior choanal atresia syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-214403170-C-T is Benign according to our data. Variant chr1-214403170-C-T is described in ClinVar as Benign. ClinVar VariationId is 1280145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005401.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN14	NM_005401.5	MANE Select	c.511-217G>A		intron	N/A	NP_005392.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN14	ENST00000366956.10	TSL:1 MANE Select	c.511-217G>A		intron	N/A	ENSP00000355923.4
	PTPN14	ENST00000543945.5	TSL:5	c.511-217G>A		intron	N/A	ENSP00000443330.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29195 AN: 151988 Hom.: 2988 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.192 AC: 29218 AN: 152106 Hom.: 2990 Cov.: 32 AF XY: 0.191 AC XY: 14242 AN XY: 74388

African (AFR) AF: 0.209 AC: 8659 AN: 41452

American (AMR) AF: 0.260 AC: 3971 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1214 AN: 5168

South Asian (SAS) AF: 0.116 AC: 560 AN: 4812

European-Finnish (FIN) AF: 0.106 AC: 1128 AN: 10604

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12237 AN: 67996

Other (OTH) AF: 0.224 AC: 473 AN: 2110

Alfa AF: 0.189 Hom.: 4646

Bravo AF: 0.208

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.84
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6657749; hg19: chr1-214576513; COSMIC: COSV107455394;